Protecting Preterm Infants From Respiratory Tract Infections and Wheeze by Using Bacterial Lysates. (PROTEA)

August 20, 2024 updated by: Gerdien Tramper, Franciscus Gasthuis

Protecting Late-moderate Preterm Infants From Respiratory Tract Infections and Wheeze in Their First Years of Life by Using Bacterial Lysates.

The primary objective of this study is to reduce respiratory tract infections and wheezing in moderate-late preterms in the first years of life by bacterial lysate administration. Next to determine the correlation of biological markers with respiratory symptoms, immune protection and treatment effect.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a randomised placebo-controlled trial including 500 otherwise healthy moderate-late preterm infants. Participants will receive bacterial lysate (OM-85/Broncho-Vaxom, 3,5mg) or placebo powder for ten days each month, from 6-10 weeks after birth until 12 months after birth. At 12 months, parents of participants are asked to join in Protea-2. If they do, participants in the treatment arm of year 1 are randomised again over placebo and OM-85 and treated until the age of 24 months. Clinical data will be continuously collected by e-Health and 3 (possibly digital) study visits; with optional biological sampling and lung function at baseline, 6 and 12 months. And in case of participation in Protea-2 also at 24 months.

Main study parameters are doctor diagnosed lower RTI and wheezing episodes in the first year of life. Biological sampling will allow investigation of immune maturation, as well as microbiome development in the respiratory tract and gut. Also, biomarkers for risk-group selection and/or treatment success will be examined.

Study Type

Interventional

Enrollment (Estimated)

500

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Netherlands
    • Zuid-Holland
      • Rotterdam, Zuid-Holland, Netherlands, 3045PM
        • Recruiting
        • Franciscus Gasthuis & Vlietland
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 month to 2 months (Child)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Gestational age at delivery between 30+0 and 35+6 weeks
  • Postnatal age at least 6 weeks at randomization & postmenstrual age at least 37 weeks
  • Written informed consent by both parents or formal caregivers

Exclusion Criteria:

  • Underlying other severe respiratory disease such as broncho-pulmonary dysplasia (unexpected in this group); hemodynamic significant cardiac disease; immunodefi-ciency; severe failure to thrive; birth asphyxia with predicted poor neurological out-come; syndrome or serious congenital disorder.
  • Lower RTI before randomization
  • Dysmaturity and/or weight < 2.5 kg at age of randomization.
  • Maternal TNF-alpha inhibitors or other immunosuppression during pregnancy and/or breastfeeding
  • Parents unable to speak and read Dutch/English language
  • Known allergic hypersensitivity to the active ingredients/substance or to any of the excipients.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Infants in this arm will be given a placebo powder from a capsule that will be indistinguishable from the active study drug.
Other: Placebo
Placebo powder from a capsule will be given, which will be indistinguishable from the active study drug.
Active Comparator: Broncho-Vaxom treatment

Infants in this arm will be given 3,5mg bacterial lysate (OM-85) 10 days per month from 6 weeks after birth until 12 months of age.

At age 12 months they will be (if informed consent for Protea-2 is provided) randomised over Broncho-Vaxom treatment and placebo again.
Drug: Broncho-Vaxom
Broncho-Vaxom is a bacterial extract comprising lyophilised fractions of 21 different inactivated bacterial strains, which are frequently causing RTI.
Other Names:
  • OM-85
  • Broncho-Vaxom concentrate (Bacterial lysate)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total number of physician diagnosed lower RTI and wheezing episodes in the first year of life
Time Frame: In the first year of life.
Recorded by frequent questionnaires
In the first year of life.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to first lower RTI or wheezing episode
Time Frame: In the first and second year of life.
Recorded by short weekly questionnaires (which will be filled in during the first year of life) and more extensive questionnaires every six months in the first and second year of life.
In the first and second year of life.
Total number of RTI
Time Frame: In the first and second year of life.
Recorded by short weekly questionnaires (which will be filled in during the first year of life) and more extensive questionnaires every six months in the first and second year of life.
In the first and second year of life.
Total number of wheezing episodes
Time Frame: In the first and second year of life.
Recorded by short weekly questionnaires (which will be filled in during the first year of life) and more extensive questionnaires every six months in the first and second year of life.
In the first and second year of life.
Distribution of viruses
Time Frame: In the first year of life.
Viruses present in the nasofarynx during complaints of lower respiratory tract infection or wheezing. Nasofaryngeal swabs will be taken in case of complaints during the first year of life. In the second year of life this will not be done.
In the first year of life.
Medication use (bronchodilators, corticosteroids, antibiotics)
Time Frame: In the first and second year of life.
Recorded by short weekly questionnaires (which will be filled in during the first year of life) and more extensive questionnaires every six months in the first and second year of life.
In the first and second year of life.
Lung function as measured by expiratory variability index (Ventica)
Time Frame: In the first year of life.
Measured at age 6-10 weeks (baseline), 6 months and 12 months in a subset of participants.
In the first year of life.
Quality of life questionnaires
Time Frame: In the first and second year of life.
Recorded by extensive questionnaires every six months in the first and second year of life.
In the first and second year of life.
(serious) adverse events
Time Frame: In the first year of life.
Will be reported by parents immediately. Respiratory episodes are not regarded as an (S)AE since these episodes comprise primary and secondary outcomes. (S)AE's are only expected in the first year of life because the treatment stops at the age of 12 months.
In the first year of life.
Serum specific IgE (allergen sensitization) at 12 months
Time Frame: At age 12 months
Total IgE and house dust mite specific IgE
At age 12 months
Infant vaccination titers at 12 months
Time Frame: At age 12 months
Vaccination titers of haemohilus influenza type B, pneumococci, tetanus
At age 12 months
Costs- and cost-effectiveness
Time Frame: In the first and second year of life.
Estimated from information from standardized questionnaires
In the first and second year of life.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Gut and respiratory microbiome composition
Time Frame: In the first year of life.
Measured from faeces and nasofaryngeal swabs taken at age 6-10 weeks, 6 months and 12 months.
In the first year of life.
Secretory IgA in saliva
Time Frame: In the first year of life
Saliva will be collected at age 6-10 weeks, 6 months and 12 months.
In the first year of life
Immune maturation: immune cells in nasal epithelium
Time Frame: In the first year of life
Collected by nasal scraping at age 6-10 weeks, 6 months and 12 months. Analysed using masscytometry.
In the first year of life
Immune maturation: chemokines and cytokines in nasal lining fluid
Time Frame: In the first year of life
Collected by nasosorption at age 6-10 weeks, 6 months and 12 months. Analysed using Luminex cyto/chemokine assay.
In the first year of life
Immune maturation: immune cells in bloodsamples
Time Frame: In the first year of life
Collected by blooddraws at age 6-10 weeks, 6 months and 12 months. Analysed using masscytometry.
In the first year of life
Serum IgE (total and specific to house dust mite)
Time Frame: At age 12 months
Measured in blood samples which will be drawn at age 12 months
At age 12 months
Immune maturation: Single cell transcriptomics
Time Frame: At age 12 months
Performed on blood drawn at age 12 months
At age 12 months
Whole blood stimulation essays
Time Frame: At age 12 months
Performed on blood drawn at age 12 months
At age 12 months
Biomarkers predictive of high morbidity and/or treatment success
Time Frame: In the first year of life.
From combined microbial and immunological data
In the first year of life.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Franciscus Gasthuis

Collaborators

Maastricht University Medical Center
Leiden University Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 18, 2022

Primary Completion (Estimated)

December 1, 2025

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

August 24, 2021

First Submitted That Met QC Criteria

September 20, 2021

First Posted (Actual)

September 30, 2021

Study Record Updates

Last Update Posted (Actual)

August 22, 2024

Last Update Submitted That Met QC Criteria

August 20, 2024

Last Verified

August 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NL76165.100.20

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Researchdata will be shared in data repositories according to the FAIR principle. Clinical data about respiratory health will be shared in the DANS repository. Inlcuding metadata which will ensure reusability. Sequencing data will be shared online in the ENA repository which will provide an unique global identifier. All used bioinformatics pipelines for data analysis will be made accessible on a GitHub account. Immunological data will be shared in NCBI Gene Expression omnibus and ImmPort. Used analysis pipelines for the transcriptomics data will also be tracked and can be shared using a Github account.

All data shared will be pneudonymized.

IPD Sharing Time Frame

Data will come available after publication of the data in articles by initating researchers.

IPD Sharing Access Criteria

Data will be available under restricted access. A request for data sharing will include at least the reason for request (for what will the receiver use the data?) and agreements about authorship.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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